Editorial
The Importance of Real-World Evidence to Inform RSV Vaccine Guidance
Anna Hung, Lona Mody
JAMA Intern Med Published Online: November 24, 2025
doi: 10.1001/jamainternmed.2025.6364
Respiratory syncytial virus (RSV) is associated with increased risks of hospitalization and death in older adults with chronic conditions. To reduce risks in this population, 3 RSV vaccines are approved in adults 60 years and older. In June 2023, the US Centers for Disease Control and Prevention recommended a single dose of any RSV vaccine to anyone 60 years and older using shared clinical decision-making. Limited vaccine uptake led this guidance to be simplified and updated 1 year later to the current recommendation of a single dose of any RSV vaccine for (1) anyone 75 years and older and (2) anyone aged 60 to 74 years who is at increased risk of severe RSV (defined as having chronic conditions, such as lung or heart disease, or living in a nursing home). Despite the updated guidance, RSV vaccine uptake remains low, with less than half of either group receiving the vaccine.1
This low uptake can be explained by various reasons including relative recency of development of the vaccine, lack of awareness of the seriousness and frequency of RSV infection, a hazy shared clinical decision-making model, access barriers, a general vaccine fatigue, and lack of clear guidance to clinicians. Real-world evidence on vaccine effectiveness and safety can help experts shape future guidance. In JAMA Internal Medicine, Bajema et al2examine the long-term effectiveness of a single RSV dose on RSV illness and associated outcomes over 2 seasons in a large population of veterans 60 years and older. The study authors found that vaccine effectiveness against documented RSV infection was 82.5% (95% CI, 77.5%-86.9%) at 1 month after vaccination and declined to 59.4% (95% CI, 55.6%-63.5%) at 18 months after vaccination. This suggests the potential need for boosters, and experts will need to evaluate this evidence carefully to update guidance.
Furthermore, this study provides evidence on subpopulations that were either excluded or had limited representation in the original clinical trials. Such populations included immunocompromised individuals and those 80 years and older. Study authors found that among 19 296 immunocompromised veterans, vaccine effectiveness, as measured based on incidence rates of documented RSV infections, was 75.2% (95% CI, 52.5%-89.3%) at 1 month after vaccination and declined to 39.7% (95% CI, 23.9%-52.7%) at 18 months after vaccination. Among 72 423 veterans 80 years and older, vaccine effectiveness was 72.3% (95% CI, 56.1%-85.6%) at 1 month after vaccination and declined to 50.4% (95% CI, 40.5%-59.8%) at 18 months after vaccination. Lower initial effectiveness in these high-risk groups has been shown before; this study extends that work by adding 1 more season of data, allowing for longer follow-up and additional vaccine recipients.3 The greater decline in vaccine effectiveness in immunocompromised individuals compared to immunocompetent individuals was similarly identified in a recent study in a nonveteran population.4
The evidence supports vaccination with RSV for persons 60 years and older. Boosters may be needed, but for now, our efforts should be focused on saving lives and decreasing disease by encouraging vaccination of persons 75 years and older and those 60 years and older with underlying health issues.
